title: HLA-E variants are associated with sustained virological response in HIV/hepatitis C virus-coinfected patients on hepatitis C virus therapy.
abstract: OBJECTIVE
  To analyze whether human leukocyte antigen (HLA)-E allelic variants are associated with and may predict response to peg-interferon (IFN) alpha and ribavirin treatment in HIV/hepatitis C virus (HCV)-coinfected patients.
  
  
  METHODS
  Retrospective follow-up study.
  
  
  METHODS
  We studied 321 naive patients who started HCV treatment. HLA-E genotyping was performed by restriction fragment length polymorphism. A sustained virological response (SVR) was defined as undetectable plasma HCV-RNA up through 24 weeks after the end of HCV treatment.
  
  
  RESULTS
  The HLA-E*0101 allele increased the odds of achieving SVR for all patients [adjusted odds ratio (aOR) = 2.03 (95% confidence interval, 95% CI = 1.35-3.06); P = 0.001], for HCV genotype (GT) 1/4 patients (aOR = 1.62 (95% CI = 1.03-2.54), P = 0.035), and for GT2/3 patients [aOR = 9.87 (95% CI = 2.47-31.89), P = 0.001]. For decision tree analysis, the SVR rate increased from 0 to 82.6% and then to 92.5% in GT2/3 patients when the count of HLA-E*0101 alleles increased. In GT1/4 patients with rs8099917 TT genotype, the SVR rate increased from 33.3 to 54.8% and then to 61.8% when the count of HLA-E*0101 alleles increased. In GT1/4 patients with rs8099917 GT/GG genotype, the SVR rate increased from 15.4 to 22% and then to 44% when the count of HLA-E*0101 alleles increased. The overall percentage of patients correctly classified was 73.2% and the area under the receiver operating characteristic curve (AUROC) was 0.803 ± 0.024.
  
  
  CONCLUSIONS
  The HLA-E*0101 allele was associated with increased odds of HCV clearance and could help to predict SVR among HIV/HCV-coinfected patients on HCV therapy. This would be helpful to avoid treatment in those less likely to respond to pegylated-interferon-alpha and ribavirin treatment.
authors.affiliation: Unidad de Coinfección HIV/Hepatitis, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda.
authors.forename: María
authors.initials: M
authors.lastname: Guzmán-Fulgencio
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.forename: Norma
authors.initials: N
authors.lastname: Rallón
authors.forename: Amanda
authors.initials: A
authors.lastname: Fernández-Rodríguez
authors.forename: Pilar
authors.initials: P
authors.lastname: Miralles
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
authors.forename: María A
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.forename: Jaime
authors.initials: J
authors.lastname: Cosín
authors.forename: José
authors.initials: J
authors.lastname: Medrano
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Álvarez
authors.forename: Juan C
authors.initials: JC
authors.lastname: López
authors.forename: José M
authors.initials: JM
authors.lastname: Benito
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D060085:Coinfection; D005260:Female; D005500:Follow-Up Studies; D060005:Genotyping Techniques; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D019562:Viral Load; D000097625:HLA-E Antigens
chemical_list: D000998:Antiviral Agents; D015395:Histocompatibility Antigens Class I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D000097625:HLA-E Antigens; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a